Would the real mccoy please stand up?

Abstract

HepatologyVolume 19, Issue 3 p. 793-794 Hepatology ElsewhereFree Access Would the real mccoy please stand up? First published: March 1994 https://doi.org/10.1002/hep.1840190338AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC. References 1 Walker JG, Doniach D, Roitt IM, et al. Serological tests in diagnosis of primary biliary cirrhosis. Lancet 1965; 1: 827. 2 Gershwin ME, Mackay IR. Primary biliary cirrhosis: paradigm or paradox for autoimmunity. Gastroenterology 1991; 100: 822. 3 Yeaman SJ, Fussey SPM, Danner DJ, et al. Primary biliary cirrhosis: identification of two major M 2 mitochondrial autoantigens. Lancet 1988; 1: 1067– 1069. 4 van de Water J, Turchany J, Leung PSC, Lake J, Munoz S, Surh CD, Coppel R, et al. Molecular mimicry in primary biliary cirrhosis: evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex, E2. J Clin Invest 1993; 91: 2653– 2664. 5 Joplin R, Lindsay JG, Johnson GD, Strain A, Neuberger JM. Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial cells in primary biliary cirrhosis. Lancet 1992; 339: 93– 94. 6 van de Water J, Ansari AA, Surh CD, Coppel R, Roche T, Bonkovsky H, Kaplan M, et al. Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response on primary biliary cirrhosis. J Immunol 1991; 146: 89– 94. 7 Hopf U, Möller B, Stemerowitz R, et al. Relation between Escherichia coli R (rough) forms in gut, lipid A in liver, and primary biliary cirrhosis. Lancet 1988; 2: 1419. 8 Burroughs AK, Rosenstein IJ, Epstein O, et al. Bacteriuria and primary biliary cirrhosis. Gut 1984; 25: 133. 9 Nickowitz RE, Worman HJ. Autoantibodies against nuclear pore membrane protein GP 210: Evidence for molecular mimicry. Hepatology 1993; 18: 109A. 10 Manns MP, Griffin KJ, Sullvan KF, Johnson EF. LKM autoantibodies recognize a short linear sequence in P 450 IID6, a cytochrome P-4450 monooxygenase. J Clin Invest 1991; 88: 1370– 1378. 11 Manns MP and Krüger M. Immunogenetics in chronic liver diseases. Gastroenterology. In press. 12 Ballardini G, Mirakian R, Bianchi FB. Aberrant expression of HLA-DR antigens on bile duct epithelium in PBC: relevance to pathogenesis. Lancet 1984; 2: 1009. Volume19, Issue3March 1994Pages 793-794 ReferencesRelatedInformation